Drug delivery device with feedback mechanism

ABSTRACT

The disclosure relates to a drug delivery device comprising:
     a case adapted to hold a medicament container,   a plunger disposed within the case and slidable from a proximal position into a distal position for delivering a medicament from the medicament container,   at least one feedback mechanism that is in operative connection with the plunger, the feedback mechanism comprising a collar, a control spring biasing the collar in a distal direction, a needle shroud, operatively axially abutting the collar in a first coupled state and prevented from axially decoupling the collar by the plunger in its proximal position, wherein the plunger, when   approaching the distal position during movement from the proximal position towards the distal position, is adapted to allow axial decoupling of the needle shroud from the collar, thus allowing for a limited axial movement of the collar relative to the needle shroud until the collar axially abuts the needle shroud in a second coupled state.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of U.S. patent applicationSer. No. 15/578,668, filed Nov. 30, 2017, which is the national stageentry of International Patent Application No. PCT/EP2016/062455, filedon Jun. 2, 2016, and claims priority to Application No. EP 15170590.2,filed in on Jun. 3, 2015, the disclosures of which are expresslyincorporated herein in entirety by reference thereto.

TECHNICAL FIELD

The disclosure relates to a drug delivery device.

BACKGROUND

Administering an injection is a process which presents a number of risksand challenges for users and healthcare professionals, both mental andphysical. Injection devices typically fall into two categories—manualdevices and autoinjectors. In a conventional manual device, manual forceis required to drive a medicament through a needle. This is typicallydone by a plunger which is continuously pressed during the injection.There are numerous disadvantages associated with this approach. Forexample, if the plunger is released prematurely, the injection will stopand may not deliver an intended dose. Furthermore, the force required topush the plunger may be too high (e.g., if the user is elderly or achild). And, aligning the injection device, administering the injection,and keeping the injection device still during the injection may requiredexterity which some patients may not have.

Autoinjector devices aim to make self-injection easier for patients. Aconventional autoinjector may provide the force for administering theinjection by a spring, and a trigger button or other mechanism may beused to activate the injection. Autoinjectors may be single-use orreusable devices.

Furthermore, it is desirable to administer the full dose in order toachieve full effectiveness of the medicament within the patient.

Thus, there remains a need for an improved drug delivery device.

SUMMARY

Certain aspects of the present disclosure can be implemented to providean improved drug delivery device.

Certain aspects of the present disclosure can be implemented as a drugdelivery device according to claim 1.

Exemplary embodiments of the disclosure are given in the dependentclaims.

According to the disclosure, a drug delivery device comprises:

-   -   a case adapted to enclose a medicament container,    -   a plunger disposed within the case and slidable from a proximal        position into a distal position for delivering a medicament from        the medicament container,    -   at least one feedback mechanism activated by movement of the        plunger, the feedback mechanism comprising a collar, a control        spring biasing the collar in a distal direction, a needle shroud        that operatively couples to the collar in a first state, the        needle shroud prevented from decoupling the collar by the        plunger being in the proximal position, wherein the plunger,        during movement from the proximal position towards the distal        position, is adapted to allow decoupling of the needle shroud        from the collar, to allow a movement of the collar relative to        the needle shroud until the collar couples to the needle shroud        in a second state.

The drug delivery device is improved due to the feedback mechanism usedfor indicating to a patient or user that the full dose of medicament wasspent.

In an exemplary embodiment the needle shroud axially couples to thecollar in the first state and in the second state.

In an exemplary embodiment, the collar comprises one or more resilientfirst snap-fit joints adapted to couple to the needle shroud in a rampengagement in the first state, the first snap-fit joints adapted toinwardly deflect due to this ramp engagement, wherein the plunger in theproximal position is adapted to inwardly support the first snap-fitjoints, preventing their inward deflection and wherein the plunger inthe distal position is axially removed from the snap-fit joints,allowing their inward deflection.

In an exemplary embodiment, the collar comprises one or more thirdcollar ribs adapted to couple to the needle shroud in the second state.

In an exemplary embodiment, the needle shroud comprises one or moreopenings adapted to allow the deflected first snap-fit joints to engagewithin the openings.

In an exemplary embodiment, the control spring is arranged as acompression spring configured to surround at least part of the collar.

In an exemplary embodiment, the control spring is proximally grounded inthe case.

In an exemplary embodiment, the drug delivery device further comprises aplunger release mechanism adapted for preventing release of the plungerwhen the needle shroud is in a distal position and adapted to releasethe plunger when the needle shroud is in a proximal position.

In an exemplary embodiment, the plunger release mechanism comprises anangled surface on the case and a rib on the plunger adapted to engagethe angled surface so that when a force in the distal direction isapplied to the plunger, the rib abuts the angled surface biasing the riband the plunger in a rotational direction, wherein the collar is adaptedto rotationally support the rib, preventing it from moving in therotational direction when the needle shroud is in the distal positionand wherein the collar is adapted to be removed from the rib, allowingit to move in the rotational direction.

In an exemplary embodiment, an inner rib is arranged on the case adaptedto rotationally support the collar, preventing it from moving in therotational direction.

In an exemplary embodiment, the drug delivery device further comprises ashroud lock mechanism adapted to lock the collar in an advancedposition.

In an exemplary embodiment, the shroud lock mechanism comprises one ormore resilient second snap-fit joints on the collar adapted to engage ina respective opening in the case, wherein the opening comprises an axialextension allowing for some free travel of the snap-fit joints, whereinthe second snap-fit joints comprise a respective angled surface adaptedto be deflected by ends of the opening for disengaging the opening,wherein a transversal proximal surface on the second snap-fit joint isadapted to proximally abut the case, preventing the collar from movingin the proximal direction.

In an exemplary embodiment, the case comprises a front case and a rearcase adapted to be coupled to each other.

In an exemplary embodiment, the front case is part of a controlsubassembly, which further comprises the needle shroud and a cap,wherein the rear case is part of a drive subassembly, which furthercomprises the plunger, a drive spring for biasing the plunger in thedistal direction, the control spring and the collar.

In an exemplary embodiment, the plunger is hollow and the drive springis arranged within the plunger.

Further scope of applicability of the present disclosure will becomeapparent from the detailed description given hereinafter. However, itshould be understood that the detailed description and specificexamples, while indicating exemplary embodiments of the disclosure, aregiven by way of illustration only, since various changes andmodifications within the spirit and scope of the disclosure will becomeapparent to those skilled in the art from this detailed description.

BRIEF DESCRIPTION OF THE FIGURES

The present disclosure will become more fully understood from thedetailed description given hereinbelow and the accompanying drawingswhich are given by way of illustration only, and thus, are not limitiveof the present disclosure, and wherein:

FIG. 1 is a perspective view of an exemplary embodiment of anauto-injector,

FIG. 2 is a perspective view of a control subassembly,

FIG. 3 is a perspective exploded view of the control subassembly,

FIG. 4 is a perspective view of a drive subassembly,

FIG. 5 is a perspective exploded view of the drive subassembly,

FIG. 6 is a schematic exploded view of the auto-injector duringassembly,

FIG. 7A is a schematic view of a plunger release mechanism in apre-assembly or pre-use state,

FIG. 7B is a schematic view of the plunger release mechanism in a stateduring extension of an injection needle,

FIG. 7C is a schematic view of the plunger release mechanism in a stateduring extension of the injection needle immediately prior to the needlereaching full insertion depth,

FIG. 7D is a schematic view of the plunger release mechanism a state atthe beginning of an injection,

FIG. 8A is a schematic view of a feedback mechanism in the pre-assemblystate,

FIG. 8B is a schematic view of the feedback mechanism in the pre-usestate,

FIG. 8C is a schematic view of the feedback mechanism in a state withthe needle at full insertion depth,

FIG. 8D is a schematic view of the feedback mechanism in a state duringtriggering of a feedback,

FIG. 8E is a schematic view of the feedback mechanism in a state at theend of dose prior to generating the feedback,

FIG. 8F is a schematic view of the feedback mechanism in a state afterhaving generated the feedback,

FIG. 9A is a schematic view of a shroud lock mechanism in a state priorto needle insertion, i.e. in a preassembly state or preuse state,

FIG. 9B is a schematic view of the shroud lock mechanism in a statebetween the beginning of the injection and the release of the feedbackmechanism,

FIG. 9C is a schematic view of the shroud lock mechanism in a state atthe end of dose after release of the feedback mechanism,

FIG. 9D is a schematic view of the shroud lock mechanism in a post-usestate,

FIG. 10 is a perspective longitudinal section of the auto-injector withthe cap removed,

FIG. 11 is a perspective longitudinal section of the auto-injector withthe needle shroud being moved in the proximal direction,

FIG. 12 is a perspective longitudinal section of the auto-injector withthe needle shroud in a proximal position,

FIG. 13 is a perspective longitudinal section of the auto-injectorduring delivery of the medicament after release of the feedbackmechanism,

FIG. 14 is a perspective longitudinal section of the auto-injector atthe end of dose prior to generation of the audible feedback,

FIG. 15 is a perspective longitudinal section of the auto-injector atthe end of dose after generation of the audible feedback, and

FIG. 16 is a perspective longitudinal section of the auto-injector withthe needle shroud extended from the case.

Corresponding parts are marked with the same reference symbols in allfigures.

DETAILED DESCRIPTION

FIG. 1 is a perspective view of an exemplary embodiment of anauto-injector 1. The auto-injector 1 comprises a case 2 comprising asleeve shaped front case 2.1 and a rear case 2.2. A cap 11 is attachedat a distal end of the case 2. A sleeve-shaped needle shroud 7 istelescoped within the case 2. The case 2 is adapted to receive amedicament container 3, such as a syringe 3, for example a glasssyringe. The medicament container is referred to hereinafter as the“syringe 3”. The syringe 3 may be a pre-filled syringe containing amedicament M and having a needle 4 arranged at a distal end of thesyringe 3. In another exemplary embodiment, the medicament container 3may be a cartridge which includes the medicament M and engages aremovable needle (e.g., by threads, snaps, friction, etc.) When theauto-injector 1 or the syringe 3 is assembled, a protective needlesheath 5 is attached to the needle 4. A stopper 6 is arranged forsealing the syringe 3 proximally and for displacing a liquid medicamentM contained in the syringe 3 through the hollow needle 4. The syringe 3is held in the case 2 and supported at its proximal end therein.

The protective needle sheath 5 may be coupled to the cap 11 so that whenthe cap 11 is removed, the protective needle sheath 5 is also removedfrom the needle 4. The cap 11 may comprise grip features forfacilitating removal of the cap 11.

The sleeve-shaped needle shroud 7 is telescoped in the distal end of thecase 2. A control spring 8 is arranged to bias the needle shroud 7 in adistal direction D against the case 2.

A drive spring 9 in the shape of a compression spring is arranged withina proximal part of the case 2. A plunger 10 serves for forwarding theforce of the drive spring 9 to the stopper 6. In an exemplaryembodiment, the plunger 10 is hollow and the drive spring 9 is arrangedwithin the plunger 10, biasing the plunger 10 in the distal direction Dagainst the rear case 2.2.

The auto-injector 1 may be divided in two subassemblies, a controlsubassembly 1.1 and a drive subassembly 1.2. This allows for improvingflexibility as to the time and location of manufacture of thesubassemblies 1.1, 1.2 and final assembly with the syringe 3.

FIG. 2 is a perspective view of the control subassembly 1.1. FIG. 3 is aperspective exploded view of the control subassembly 1.1. The controlsubassembly 1.1 comprises all parts and mechanisms which control accessto the needle 4 and the forces a user will feel when they use theauto-injector 1. The control subassembly 1.1 comprises the cap 11, theneedle shroud 7 and the front case 2.1.

FIG. 4 is a perspective view of the drive subassembly 1.2. FIG. 5 is aperspective exploded view of the drive subassembly 1.2. The drivesubassembly 1.2 comprises the components required to deliver themedicament M. If the viscosity or volume of the medicament M in thesyringe 3 is varied, only parts of the drive subassembly 1.2 may need tobe changed. The drive subassembly 1.2 comprises the plunger 10, thedrive spring 9, the rear case 2.2, the control spring 8 and a sleeveshaped collar 14 which will be explained in more detail below.

FIG. 6 is a schematic exploded view of the auto-injector 1 duringassembly. In order to assemble the auto-injector 1, a syringe 3 with anattached needle 4 and a protective needle sheath (not illustrated) isinserted into the control subassembly 1.1 in the distal direction D.Afterwards, the drive subassembly 1.2 is inserted into the controlsubassembly 1.1 in the distal direction D.

A plunger release mechanism 12 is schematically illustrated in fourdifferent states in FIGS. 7A to 7D. The plunger release mechanism 12 isarranged for preventing release of the plunger 10 prior to depression ofthe needle shroud 7 and for releasing the plunger 10 once the needleshroud 7 is sufficiently depressed.

The plunger release mechanism 12 is adapted to control the automatedactivation of syringe emptying. The plunger release mechanism 12 isactivated immediately prior to full needle insertion. The plungerrelease mechanism 12 comprises the plunger 10, a longitudinal inner rib2.3 on the rear case 2.2 and the collar 14. The needle shroud 7, notrepresented in FIGS. 7A to 7D, is coupled to the collar 14 and adaptedto push the collar 14 in a proximal direction P.

The needle shroud 7, the rear case 2.2 and its inner rib 2.3, and thecollar 14 are configured to move only in an axial direction, i.e. in thedistal direction D and the proximal direction P, whereas the plunger 10can both move rotationally in rotational directions R1, R2 and axiallyin the distal direction D and the proximal direction P. In an exemplaryembodiment, there may be no compliant part in the plunger releasemechanism 12, i.e. the parts may be all rigid and move as a whole withno relative deformation within a part.

FIG. 7A shows the plunger release mechanism 12 in a pre-assembly orpre-use state with the plunger 10 in a proximal position P1. Theconfiguration of the plunger release mechanism 12 does not change whentransitioning from the pre-assembly state to the pre-use state, i. e.assembling the control sub-assembly 1.1 and the drive sub-assembly 1.2does not impact the plunger release mechanism 12.

In the pre-assembly or pre-use state, a rib 10.1 on the plunger 10 isslid in an opening 2.4 within the rear case 2.2. The opening 2.4 has anangled surface 2.5 so that when a force in the distal direction D isapplied to the plunger 10, e.g. by the drive spring 9, the rib 10.1abuts the angled surface 2.5 and the plunger 10 attempts to rotate inthe rotational direction R1. The rib 10.1 is prevented to move along theangled surface 2.5 of the opening 2.4 by a first collar rib 14.1 on thecollar 14. The collar 14 is prevented from rotating in the rotationaldirection R1 by the inner rib 2.3 on the rear case 2.2.

FIG. 7B shows the plunger release mechanism 12 in a state duringextension of the injection needle 4. The needle shroud 7 is moved in theproximal direction P into the front case 2.1, e.g. by a user pressingthe shroud against an injection site, thereby inserting the needle 4into the injection site. As the needle shroud 7 is coupled to the collar14, the collar 14 moves in the proximal direction P as well. The firstcollar rib 14.1 moves in the proximal direction P accordingly, beginningto clear the way for the rib 10.1 of the plunger 10.

FIG. 7C shows the plunger release mechanism 12 in a state duringextension of the injection needle 4 immediately prior to the needle 4reaching full insertion depth. The first collar rib 14.1 has been movedfurther in the proximal direction P and disengages the rib 10.1 on theplunger 10 so that the plunger 10 is no longer prevented from rotatingin the rotational direction R1. The rib 10.1 on the plunger 10 is freeto slide along the angled surface 2.5 of the opening 2.4 in the rearcase 2.2.

FIG. 7D shows the plunger release mechanism 12 in a state at thebeginning of an injection. The rib 10.1 on the plunger 10 finishes itscourse along the angled surface 2.5 of the opening 2.4 in the rear case2.2, thus becoming able to move in the distal direction D without beingfurther rotated. Under the action of the drive spring 9, the plunger 10pushes on the stopper 6 and starts to empty the content of the syringe3.

A feedback mechanism 13 is arranged for enabling emission of an audibleand/or tactile feedback indicating the completion of medicamentdelivery. The feedback mechanism 13 is schematically illustrated in sixdifferent states in FIGS. 8A to 8F.

The feedback mechanism 13 comprises the plunger 10, the rear case 2.2,the needle shroud 7, the collar 14 and the control spring 8.

FIG. 8A shows the feedback mechanism 13 in the pre-assembly state. Onlythe drive sub-assembly 1.2 is represented in this state. The controlspring 8 is compressed between two second collar ribs 14.2 on the collar14 and a proximal end 2.6 of the rear case 2.2. The plunger 10 isarranged within the collar 14 between inner protrusions 14.4 of firstsnap-fit joints 14.3 on the collar 14. Consequently, the first snap-fitjoints 14.3 cannot deflect inward under the force of the control spring8 pushing in the distal direction D.

FIG. 8B shows the feedback mechanism 13 in the pre-use state. Thecontrol subassembly 1.1 is pushed into the drive sub-assembly 1.2. Thefront case 2.1 and the rear case 2.2 may be coupled by two clips on thefront case 2.1 getting caught within openings in the rear case 2.2 (notrepresented) or vice versa. The needle shroud 7 is inserted and proximalarms 7.1 on the needle shroud 7 axially abut the first snap-fit joints14.3.

FIG. 8C shows the feedback mechanism 13 in a state with the needle 4 atfull insertion depth. The needle shroud 7 has been fully moved in theproximal direction P, e.g. by pushing it against an injection site, andhas dragged along the collar 14 in the proximal direction P, compressingthe control spring 8. As the plunger 10 is arranged within the collar 14between the inner protrusions 14.4 of the first snap-fit joints 14.3,the first snap-fit joints 14.3 cannot deflect inward under the force ofthe control spring 8 pushing in the distal direction D.

FIG. 8D shows the feedback mechanism 13 in a state when the feedback istriggered near the end of medicament dispense. The plunger 10,approaching the end of its travel with the stopper 6 having nearlybottomed out in the syringe 3, slides down inward angled surfaces 14.5on the inner protrusions 14.4 allowing for inward deflection of thefirst snap-fit joints 14.3. Due to a ramp engagement between the firstsnap-fit joints 14.3 and the proximal ends of the proximal arms 7.1 ofthe collar 14, the first snap-fit joints 14.3 are inwardly deflecteddriven by the control spring 8 disengaging them from their axialabutment with the proximal arms 7.1, moving them between the proximalarms 7.1.

FIG. 8E shows the feedback mechanism 13 in a state at the end of doseprior to generating the feedback. The plunger 10 at least almostfinishes emptying the syringe 3 and is completely removed from betweenthe first snap-fit joints 14.3. In the meantime, the collar 14 hastravelled further in the distal direction D along the proximal arms 7.1and the two first snap-fit joints 14.3 have arrived at respectiveopenings 7.2 in the proximal arms 7.1, allowing the first snap-fitjoints 14.3 to relax and straighten back to their initial shape withinand engage within the openings 7.2 in the proximal arms 7.1.

FIG. 8F shows the feedback mechanism 13 in a state at the end of dose Fafter having generated the feedback. Due to the relaxed first snap-fitjoints 14.3 being engaged within the openings 7.2 whose longitudinalextension allows for some free travel of the first snap-fit joints 14.3,the friction acting against the control spring 8 is reduced and thecontrol spring 8 can now expand and drive the collar 14 in the distaldirection D along the proximal arms 7.1 of the needle shroud 7 until twothird collar ribs 14.6 on the collar 14 axially hit the proximal arms7.1 of the needle shroud 7, thus creating an audible and/or tactilefeedback which indicates that the dose is complete.

FIGS. 9A to 9D show schematic views of a shroud lock mechanism 15 infour different states. The shroud lock mechanism 15 is arranged to lockthe needle shroud 7 after removal of the auto-injector 1 from aninjection site post-use and consequent translation of the needle shroud7 in the distal direction D relative the case 2.

The shroud lock mechanism 15 comprises the rear case 2.2 and the collar14.

FIG. 9A shows the shroud lock mechanism 15 in a state prior to needleinsertion, i.e. in a preassembly state or pre-use state. Two secondsnap-fit joints 14.7 are arranged on the collar 14 and rest in twoopenings 2.8 in distal arms 2.9 on the rear case 2.2.

FIG. 9B shows the shroud lock mechanism 15 in a state between thebeginning of the injection and the release of the feedback mechanism 13(both states included). The needle shroud 7 and the collar 14 moved inthe proximal direction P as the needle shroud 7 was pushed against theinjection site. The two second snap-fit joints 14.7 move in the proximaldirection P accordingly, travelling up the openings 2.8 whose axialextension allows for some free travel.

FIG. 9C shows the shroud lock mechanism 15 in a state at the end of doseafter release of the feedback mechanism 13. As the feedback mechanism 13is released, the collar 14 moves in the distal direction D (cf. FIG.8F). The two second snap-fit joints 14.7 move in the distal direction Daccordingly, travelling down the openings 2.8 in the distal arms 2.9 ofthe rear case 2.2.

FIG. 9D shows the shroud lock mechanism 15 in a post-use state. Once themedicament injection is complete, the user pulls the auto-injector 1away from the injection site and the needle shroud 7 is forced out ofthe case 2 in the distal direction D by the control spring 8, envelopingthe needle 4 and thus acting as a protective shell around it (notrepresented). The collar 14 is arranged between the needle shroud 7 andthe control spring 8. Following the motion of the needle shroud 7, thecollar 14 moves in the distal direction D as well. The two secondsnap-fit joints 14.7 move accordingly and are deflected inward withinthe rear case 2.2 as angled surfaces 14.8 on the second snap-fit joints14.7 engage the distal ends of the openings 2.8. As the second snap-fitjoints 14.7 travel further beyond the distal ends of the distal arms 2.9on the rear case 2.2, they are allowed to relax and straighten backoutwards to their initial shape. The collar 14 is in an advancedposition A and the needle shroud 7, coupled to the collar 14, is in itsdistal position S1. If it is attempted to push the needle shroud 7 inthe proximal direction P again, transversal proximal surfaces 14.9 onthe second snap-fit joints 14.7 proximally abut the distal arms 2.9 ofthe rear case 2.2 preventing further depression of the needle shroud 7and re-exposure of the needle 4.

A sequence of operation of the auto-injector 1 is as follows:

The auto-injector 1 is initially in the state as shown in FIG. 1. Theplunger release mechanism 12 is in the pre-use state as shown in FIG.7A. The feedback mechanism 13 is in the pre-use state as illustrated inFIG. 8B. The shroud lock mechanism 15 is in the pre-use state asillustrated in FIG. 9A.

The user removes the cap 11 pulling it in the distal direction D awayfrom the case 2. The protective needle sheath 5 may be coupled to thecap 11 so that when the cap 11 is removed, the protective needle sheath5 is also removed from the needle 4. FIG. 10 is a perspectivelongitudinal section of the auto-injector 1 with the cap 11 removed. Theneedle shroud 7 is in a distal position S1.

FIG. 11 is a perspective longitudinal section of the auto-injector 1with the needle shroud 7 being moved in the proximal direction P, e.g.by placing it against the injection site and sliding the case 2forwards. The control spring 8 is held between the collar 14 and therear case 2.2 and is further compressed when the case 2 moves forwardsrelative to the needle shroud 7. Except for the needle shroud 7 and thecollar 14, all components of the auto-injector 1 move with the case 2.The needle shroud 7 and the collar 14, axially coupled as shown in FIG.8B, move in the proximal direction P in comparison to the rest of theparts of the auto-injector 1, thus initiating the plunger releasemechanism 12. The plunger release mechanism 12 thus arrives in the stateas illustrated in FIG. 7B. The feedback mechanism 13 transitions fromthe pre-use state shown in FIG. 8B to the state as illustrated in FIG.8C. The shroud lock mechanism 15 transitions from the pre-use state ofFIG. 9A to the state as illustrated in FIG. 9B.

FIG. 12 is a perspective longitudinal section of the auto-injector 1with the needle shroud 7 being fully moved in the proximal direction Pinto a proximal position S2 such that the needle 4 has reached theinsertion depth in the injection site. Once the needle shroud 7 is fullydepressed, the plunger 10 releases as shown in FIG. 7D and medicamentdelivery begins. The drive spring 9 begins to expand, pushing theplunger 10 in the distal direction D to inject the medicament M. Thefeedback mechanism 13 is in the state as illustrated in FIG. 8C. Theshroud lock mechanism 15 is in the state as illustrated in FIG. 9B.

FIG. 13 is a perspective longitudinal section of the auto-injector 1during delivery of the medicament M after release of the feedbackmechanism 13. As the delivery of the medicament M progresses with theplunger 10 moving down the syringe 3 barrel, the feedback mechanism 13activates. Up to this point, the collar 14 was resting on the needleshroud 7, the needle shroud 7 preventing the collar 14 from movingfurther in the distal direction D. Prior to the end of the dose, theplunger 10 clears the inside of the collar 14, leaving the two firstsnap-fit joints 14.3 free to deflect inward. Under the force of thecontrol spring 8, the collar 14 moves in the distal direction D, forcingits way in between the proximal arms 7.1 on the needle shroud 7. The twofirst snap fit joints 14.3 are deflected inward within the needle shroud7. The feedback mechanism 13 arrives in the state as illustrated in FIG.8D. The shroud lock mechanism 15 is in the state as illustrated in FIG.9B.

FIG. 14 is a perspective longitudinal section of the auto-injector 1 atthe end of dose prior to generation of the audible feedback. The plunger10 has fully advanced the stopper 6 within the syringe 3 barrel andarrived at a distal position P2. Pursuing its course, the collar 14brings the two first snap-fit joints 14.3 down to the opening 7.2 in theneedle shroud 7, where the first snap-fit joints 14.3 straighten back totheir initial shape. The feedback mechanism 13 arrives in the state asillustrated in FIG. 8E.

FIG. 15 is a perspective longitudinal section of the auto-injector 1 atthe end of dose after generation of the audible feedback. The injectionis complete and an audible and/or tactile feedback is emitted throughthe collar 14 hitting the needle shroud 7 as the feedback mechanism 13operates. With reduced friction, the collar 14 is propelled by thecontrol spring 8 and the two third collar ribs 14.6 hit the needleshroud 7, creating the noise indicating that the dose is complete. Thefeedback mechanism 13 arrives in the state as illustrated in FIG. 8F.The shroud lock mechanism 15 is in the state as illustrated in FIG. 9C.

FIG. 16 is a perspective longitudinal section of the auto-injector 1post-use with the needle shroud 7 extended from the case 2. As theauto-injector 1 is moved away from the injection site, the needle shroud7 and the collar 14, which are axially coupled as shown in FIG. 8F,advance, driven by the control spring 8. The needle shroud 7 returns toits pre-use position. However, the position of the collar 14 has evolvedsince the pre-use state. The two second snap-fit joints 14.7, which wereso far travelling within the opening 2.8 in the rear case 2.2, movefurther in the distal direction D and take position just beneath thedistal arms 2.9 of the rear case 2.2. This suppresses the axial degreeof freedom of the collar 14 and the needle shroud 7, which are bothstill axially coupled. The collar 14 is locked and prevents any furtheraxial motion of the needle shroud 7, rendering the auto-injector 1needle safe in its post-use state. The shroud lock mechanism 15 is inthe state as illustrated in FIG. 9D.

The case 2 may comprise a viewing window (not illustrated) allowing theuser to examine the medicament M for clarity, observe the advancingplunger 10 for allowing to estimate the progress of the medicamentdelivery, and helping the user differentiate between a used and anun-used auto-injector 1.

In an exemplary embodiment, a tamper strip may be arranged between thecap 11 and the front case 2.1 when the control subassembly 1.1 isassembled.

The auto-injector 1 may be placed against the injection site multipletimes without any adverse effect to the mechanism. The force to depressthe needle shroud 7 may be less than 6 N.

The syringe 3 used in the auto-injector 1 may for example be a 1 mlsyringe 3.

The auto-injector 1 is always needle safe as the needle can be retractedbefore the delivery of the medicament M is complete.

As only the plunger 10 and the rear case 2.2 are subjected to therelatively high force of the drive spring 9, the other components of theauto-injector 1 are not affected, so reliability and shelf life areincreased.

The auto-injector 1 is suited to be used as a platform as the drivespring 9 can be swapped to deliver different viscosity drugs withoutaffecting the insertion or retraction functions. This is particularlyadvantageous for high viscosity fluids.

The terms “drug” or “medicament” are used herein to describe one or morepharmaceutically active compounds. As described below, a drug ormedicament can include at least one small or large molecule, orcombinations thereof, in various types of formulations, for thetreatment of one or more diseases. Exemplary pharmaceutically activecompounds may include small molecules; polypeptides, peptides andproteins (e.g., hormones, growth factors, antibodies, antibodyfragments, and enzymes); carbohydrates and polysaccharides; and nucleicacids, double or single stranded DNA (including naked and cDNA), RNA,antisense nucleic acids such as antisense DNA and RNA, small interferingRNA (siRNA), ribozymes, genes, and oligonucleotides. Nucleic acids maybe incorporated into molecular delivery systems such as vectors,plasmids, or liposomes. Mixtures of one or more of these drugs are alsocontemplated.

The term “drug delivery device” shall encompass any type of device orsystem configured to dispense a drug into a human or animal body.Without limitation, a drug delivery device may be an injection device(e.g., syringe, pen injector, auto injector, large-volume device, pump,perfusion system, or other device configured for intraocular,subcutaneous, intramuscular, or intravascular delivery), skin patch(e.g., osmotic, chemical, micro-needle), inhaler (e.g., nasal orpulmonary), implantable (e.g., coated stent, capsule), or feedingsystems for the gastro-intestinal tract. The presently described drugsmay be particularly useful with injection devices that include a needle,e.g., a small gauge needle.

The drug or medicament may be contained in a primary package or “drugcontainer” adapted for use with a drug delivery device. The drugcontainer may be, e.g., a cartridge, syringe, reservoir, or other vesselconfigured to provide a suitable chamber for storage (e.g., short- orlong-term storage) of one or more pharmaceutically active compounds. Forexample, in some instances, the chamber may be designed to store a drugfor at least one day (e.g., 1 to at least 30 days).

In some instances, the chamber may be designed to store a drug for about1 month to about 2 years. Storage may occur at room temperature (e.g.,about 20° C.), or refrigerated temperatures (e.g., from about −4° C. toabout 4° C.). In some instances, the drug container may be or mayinclude a dual-chamber cartridge configured to store two or morecomponents of a drug formulation (e.g., a drug and a diluent, or twodifferent types of drugs) separately, one in each chamber. In suchinstances, the two chambers of the dual-chamber cartridge may beconfigured to allow mixing between the two or more components of thedrug or medicament prior to and/or during dispensing into the human oranimal body. For example, the two chambers may be configured such thatthey are in fluid communication with each other (e.g., by way of aconduit between the two chambers) and allow mixing of the two componentswhen desired by a user prior to dispensing. Alternatively or inaddition, the two chambers may be configured to allow mixing as thecomponents are being dispensed into the human or animal body.

The drug delivery devices and drugs described herein can be used for thetreatment and/or prophylaxis of many different types of disorders.Exemplary disorders include, e.g., diabetes mellitus or complicationsassociated with diabetes mellitus such as diabetic retinopathy,thromboembolism disorders such as deep vein or pulmonarythromboembolism. Further exemplary disorders are acute coronary syndrome(ACS), angina, myocardial infarction, cancer, macular degeneration,inflammation, hay fever, atherosclerosis and/or rheumatoid arthritis.

Exemplary drugs for the treatment and/or prophylaxis of diabetesmellitus or complications associated with diabetes mellitus include aninsulin, e.g., human insulin, or a human insulin analogue or derivative,a glucagon-like peptide (GLP-1), GLP-1 analogues or GLP-1 receptoragonists, or an analogue or derivative thereof, a dipeptidyl peptidase-4(DPP4) inhibitor, or a pharmaceutically acceptable salt or solvatethereof, or any mixture thereof. As used herein, the term “derivative”refers to any substance which is sufficiently structurally similar tothe original substance so as to have substantially similar functionalityor activity (e.g., therapeutic effectiveness).

Exemplary insulin analogues are Gly(A21), Arg(B31), Arg(B32) humaninsulin (insulin glargine); Lys(B3), Glu(B29) human insulin; Lys(B28),Pro(B29) human insulin; Asp(B28) human insulin; human insulin, whereinproline in position B28 is replaced by Asp, Lys, Leu, Val or Ala andwherein in position B29 Lys may be replaced by Pro; Ala(B26) humaninsulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30)human insulin.

Exemplary insulin derivatives are, for example, B29-N-myristoyl-des(B30)human insulin; B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoylhuman insulin; B29-N-palmitoyl human insulin; B28-N-myristoylLysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin;B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30human insulin; B29-N—(N-palmitoyl-gamma-glutamyl)-des(B30) humaninsulin; B29-N—(N-lithocholyl-gamma-glutamyl)-des(B30) human insulin;B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin andB29-N-(ω-carboxyheptadecanoyl) human insulin. Exemplary GLP-1, GLP-1analogues and GLP-1 receptor agonists are, for example:Lixisenatide/AVE0010/ZP10/Lyxumia,Exenatide/Exendin-4/Byetta/Bydureon/ITCA 650/AC-2993 (a 39 amino acidpeptide which is produced by the salivary glands of the Gila monster),Liraglutide/Victoza, Semaglutide, Taspoglutide, Syncria/Albiglutide,Dulaglutide, rExendin-4, CJC-1134-PC, PB-1023, TTP-054,Langlenatide/HM-11260C, CM-3, GLP-1 Eligen, ORMD-0901, NN-9924, NN-9926,NN-9927, Nodexen, Viador-GLP-1, CVX-096, ZYOG-1, ZYD-1, GSK-2374697,DA-3091, MAR-701, MAR709, ZP-2929, ZP-3022, TT-401, BHM-034. MOD-6030,CAM-2036, DA-15864, ARI-2651, ARI-2255, Exenatide-XTEN andGlucagon-Xten.

An exemplary oligonucleotide is, for example: mipomersen/Kynamro, acholesterol-reducing antisense therapeutic for the treatment of familialhypercholesterolemia.

Exemplary DPP4 inhibitors are Vildagliptin, Sitagliptin, Denagliptin,Saxagliptin, Berberine.

Exemplary hormones include hypophysis hormones or hypothalamus hormonesor regulatory active peptides and their antagonists, such asGonadotropine (Follitropin, Lutropin, Choriongonadotropin, Menotropin),Somatropine (Somatropin), Desmopressin, Terlipressin, Gonadorelin,Triptorelin, Leuprorelin, Buserelin, Nafarelin, and Goserelin.

Exemplary polysaccharides include a glucosaminoglycane, a hyaluronicacid, a heparin, a low molecular weight heparin or an ultra-lowmolecular weight heparin or a derivative thereof, or a sulphatedpolysaccharide, e.g. a poly-sulphated form of the above-mentionedpolysaccharides, and/or a pharmaceutically acceptable salt thereof. Anexample of a pharmaceutically acceptable salt of a poly-sulphated lowmolecular weight heparin is enoxaparin sodium. An example of ahyaluronic acid derivative is Hylan G-F 20/Synvisc, a sodiumhyaluronate.

The term “antibody”, as used herein, refers to an immunoglobulinmolecule or an antigen-binding portion thereof. Examples ofantigen-binding portions of immunoglobulin molecules include F(ab) andF(ab′)₂ fragments, which retain the ability to bind antigen. Theantibody can be polyclonal, monoclonal, recombinant, chimeric,de-immunized or humanized, fully human, non-human, (e.g., murine), orsingle chain antibody. In some embodiments, the antibody has effectorfunction and can fix complement. In some embodiments, the antibody hasreduced or no ability to bind an Fc receptor. For example, the antibodycan be an isotype or subtype, an antibody fragment or mutant, which doesnot support binding to an Fc receptor, e.g., it has a mutagenized ordeleted Fc receptor binding region.

The terms “fragment” or “antibody fragment” refer to a polypeptidederived from an antibody polypeptide molecule (e.g., an antibody heavyand/or light chain polypeptide) that does not comprise a full-lengthantibody polypeptide, but that still comprises at least a portion of afull-length antibody polypeptide that is capable of binding to anantigen. Antibody fragments can comprise a cleaved portion of a fulllength antibody polypeptide, although the term is not limited to suchcleaved fragments. Antibody fragments that are useful in the presentdisclosure include, for example, Fab fragments, F(ab′)2 fragments, scFv(single-chain Fv) fragments, linear antibodies, monospecific ormultispecific antibody fragments such as bispecific, trispecific, andmultispecific antibodies (e.g., diabodies, triabodies, tetrabodies),minibodies, chelating recombinant antibodies, tribodies or bibodies,intrabodies, nanobodies, small modular immunopharmaceuticals (SMIP),binding-domain immunoglobulin fusion proteins, camelized antibodies, andVHH containing antibodies. Additional examples of antigen-bindingantibody fragments are known in the art.

The terms “Complementarity-determining region” or “CDR” refer to shortpolypeptide sequences within the variable region of both heavy and lightchain polypeptides that are primarily responsible for mediating specificantigen recognition. The term “framework region” refers to amino acidsequences within the variable region of both heavy and light chainpolypeptides that are not CDR sequences, and are primarily responsiblefor maintaining correct positioning of the CDR sequences to permitantigen binding. Although the framework regions themselves typically donot directly participate in antigen binding, as is known in the art,certain residues within the framework regions of certain antibodies candirectly participate in antigen binding or can affect the ability of oneor more amino acids in CDRs to interact with antigen.

Exemplary antibodies are anti PCSK-9 mAb (e.g., Alirocumab), anti IL-6mAb (e.g., Sarilumab), and anti IL-4 mAb (e.g., Dupilumab).

The compounds described herein may be used in pharmaceuticalformulations comprising (a) the compound(s) or pharmaceuticallyacceptable salts thereof, and (b) a pharmaceutically acceptable carrier.The compounds may also be used in pharmaceutical formulations thatinclude one or more other active pharmaceutical ingredients or inpharmaceutical formulations in which the present compound or apharmaceutically acceptable salt thereof is the only active ingredient.Accordingly, the pharmaceutical formulations of the present disclosureencompass any formulation made by admixing a compound described hereinand a pharmaceutically acceptable carrier.

Pharmaceutically acceptable salts of any drug described herein are alsocontemplated for use in drug delivery devices. Pharmaceuticallyacceptable salts are for example acid addition salts and basic salts.Acid addition salts are e.g. HCl or HBr salts. Basic salts are e.g.salts having a cation selected from an alkali or alkaline earth metal,e.g. Na+, or K+, or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), whereinR1 to R4 independently of each other mean: hydrogen, an optionallysubstituted C1-C6-alkyl group, an optionally substituted C2-C6-alkenylgroup, an optionally substituted C6-C10-aryl group, or an optionallysubstituted C6-C10-heteroaryl group. Further examples ofpharmaceutically acceptable salts are known to those of skill in thearts.

Pharmaceutically acceptable solvates are for example hydrates oralkanolates such as methanolates or ethanolates.

Those of skill in the art will understand that modifications (additionsand/or removals) of various components of the substances, formulations,apparatuses, methods, systems and embodiments described herein may bemade without departing from the full scope and spirit of the presentdisclosure, which encompass such modifications and any and allequivalents thereof.

LIST OF REFERENCES

-   -   1 auto-injector    -   1.1 control subassembly    -   1.2 drive subassembly    -   2 case    -   2.1 front case    -   2.2 rear case    -   2.3 inner rib    -   2.4 opening    -   2.5 angled surface    -   2.6 proximal end    -   2.8 opening    -   2.9 distal arm    -   3 syringe    -   4 injection needle    -   5 protective needle sheath    -   6 stopper    -   7 needle shroud    -   7.1 proximal arm    -   7.2 opening    -   8 control spring    -   9 drive spring    -   10 plunger    -   10.1 rib    -   11 cap    -   12 plunger release mechanism    -   13 feedback mechanism    -   14 collar    -   14.1 first collar rib    -   14.2 second collar rib    -   14.3 first snap-fit joint    -   14.4 inner protrusion    -   14.5 angled surface    -   14.6 third collar rib    -   14.7 second snap-fit joint    -   14.8 angled surface    -   14.9 proximal surface    -   15 shroud lock mechanism    -   A advanced position    -   D distal direction    -   M medicament    -   P proximal direction    -   P1 proximal position    -   P2 distal position    -   R1 rotational direction    -   R2 rotational direction    -   S1 distal position    -   S2 proximal position

1-14. (canceled)
 15. A drug delivery device comprising: a case adapted to receive at least a portion of a medicament container; a plunger movable relative to the case in a distal direction away from a proximal position for delivering a medicament from the medicament container; a collar axially displaceable relative to the case away from a first position; a plunger release mechanism to release the plunger for delivering the medicament from the medicament container; a release member arranged to operatively couple to the collar in the first position, wherein the release member is movable relative to the case, wherein the plunger release mechanism is configured to release the plunger for delivering the medicament from the medicament container when the release member is moved into a release position relative to the case, and wherein the collar is in the first position when the plunger is in the proximal position.
 16. The drug delivery device of claim 15, wherein the collar is operatively coupled to the plunger and, in the first position, the collar is configured to prevent the plunger from moving away from the proximal position.
 17. The drug delivery device of claim 16, wherein the plunger is configured to be released and move in the distal direction when the collar is displaced away from the first position.
 18. The drug delivery device of claim 17, wherein the release member is adapted to push the collar in a proximal direction.
 19. The drug delivery device of claim 15, wherein the release member is telescoped in a distal end of the case, and wherein a control spring is arranged to bias the release member in the distal direction against the case.
 20. The drug delivery device of claim 19, wherein the release member is a needle shroud.
 21. The drug delivery device of claim 20, wherein the drug delivery device comprises a shroud lock mechanism configured to prevent proximal movement of the needle shroud in a post-use state of the drug delivery device.
 22. The drug delivery device of claim 21, wherein the shroud lock mechanism comprises the collar.
 23. The drug delivery device of claim 15, wherein there is no compliant part in the plunger release mechanism.
 24. The drug delivery device of claim 15, further comprising a rib, wherein the case comprises an angled surface such that when a force in the distal direction is applied to the plunger, the rib abuts the angled surface and a rotational force is applied to the plunger.
 25. The drug delivery device of claim 24, wherein the rib is a rib of the plunger.
 26. The drug delivery device of claim 24, wherein the force in the distal direction is applied by a drive spring.
 27. The drug delivery device of claim 24, wherein the rib is prevented from moving along the angled surface by a collar rib on the collar.
 28. The drug delivery device of claim 15, wherein the plunger is arranged within the collar.
 29. A drug delivery device comprising: a case adapted to receive at least a portion of a medicament container; a plunger movable relative to the case in a distal direction away from a proximal position for delivering a medicament from the medicament container; a collar axially displaceable relative to the case away from a first position; a needle shroud arranged to operatively couple to the collar in the first position, wherein the collar is in the first position when the plunger is in the proximal position.
 30. The drug delivery device of claim 29, wherein the collar is operatively coupled to the plunger and, in the first position, the collar is configured to prevent the plunger from moving away from the proximal position, and the plunger is configured to be released and move in the distal direction when the collar is displaced away from the first position.
 31. The drug delivery device of claim 29, wherein the needle shroud is telescoped in a distal end of the case, and a control spring is arranged to bias the needle shroud in the distal direction against the case.
 32. The drug delivery device of claim 29, wherein the drug delivery device comprises a shroud lock mechanism configured to prevent proximal movement of the needle shroud in a post-use state of the drug delivery device, and the shroud lock mechanism comprises the collar.
 33. The drug delivery device of claim 29, wherein the plunger comprises a rib, and the case comprises an angled surface such that when a force in the distal direction is applied to the plunger, the rib abuts the angled surface and a rotational force is applied to the plunger.
 34. The drug delivery device of claim 29, further comprising the medicament container disposed in the case, the medicament container containing the medicament. 